‘Sweeter’ than its name: anti-inflammatory activities of Stevia rebaudiana

Figures & data

Figure 1. General information about native South American plant, S. rebaudiana, and its anti-inflammatory activity (adapted from Ferrazzano et al. 2015). The colored regions on the map show cultivation sites of S. rebaudiana.

Table 1. Botanical classification and morphological features of Stevia rebaudiana (modified from Gutiérrez et al. (2016)).

		Description
Botanical classification	Kingdom	Plantae
	Subkingdom	Tracheobionta
	Superdivision	Sprematophyta
	Division	Magnoliophyta
	Class	Magnoliopside
	Subclass	Asteridae
	Group	Monochlamydae
	Order	Asterales
	Family	Asteraceae (formerly Compositae)
	Subfamily	Asteroideae
	Tribe	Eupatorieae
	Genus	Stevia
	Species	rebaudiana
Morphological features	Leaves	Petiole: present, absent; Shape: linear, oblong, elliptical, ovate, rhombic; Margin: entire, subentire, crenate, serrate, dentate; Glands: glandular trichomes
	Flowers	Peduncles: shortly pedunculate, sessile; Shape: funnelform; Involucre: cylindrical; Number: 5–6; Color: white, pink, purple

Table 2. Steviol glycosides present in S. rebaudiana leaves (LOD, limit of detection).

			Amount of steviol glycosides (mg/g DW)
			Aranda-González et al. (2015)	Periche et al. (2015)	Lemus-Mondaca et al. (2016)	Wald and Morlock (2017)	Debnath et al. (2018)	Kovačević et al. (2018)	Formigoni et al. (2018)	Gardana and Simonetti (2018)	Gomes et al. (2018)	Elhassaneen (2019)
Steviol glycosides	Chemical formula	Molar mass (g/mol)	Mexico	Germany	Chile	Germany	India^a	Croatia	Brazil	Italy^b	Brazil	Egypt
Stevioside	C38H60O18	804.87	–	46.48	34.4 ± 1.4	95 ± 4.0	16.3 ± 1.2	74.9 ± 1.2–90.9 ± 1.3	40.95 ± 1.72	0.2 ± 0.01–481.0 ± 17.0	57.09	88.7 ± 12.8
Steviol			–	–	–	–	–	–	–	–	–	–
Steviolbioside	C32H50O13	642.73	3.5 ± 0.2–5.8 ± 0.1	–	20.1 ± 0.8	2.0 ± 0.0	–	–	–	0.1 ± 0.03–21.0 ± 0.7	–	–
Rebaudioside A	C44H70O23	967.01	–	17.03	11.6 ± 0.5	23.0 ± 0.0	6.86 ± 0.61	21.2 ± 0.4–32.2 ± 1.6	44.1 ± 1.85	233.0 ± 9.0–994.0 ± 32.0	25.86	26.5 ± 2.4
Rebaudioside B^c	C38H60O18	804.87	2.7 ± 0.1–6.5 ± 0.2	–	1.1 ± 0.0	< LOD	–	–		0.1 ± 0.0–256.0 ± 8.0	–	–
Rebaudioside C	C44H70O22	951.01	20.5 ± 0.1–22.4 ± 0.4	6.6	1.6 ± 0.0	< LOD	–	–	19.91 ± 0.80	0.1 ± 0.0–154.0 ± 5.0	–	4.3 ± 1.1
Rebaudioside D	C50H80O28	1129.15	–	–	–	< LOD	–	–	–	0.1 ± 0.0–21.0 ± 0.70	–	–
Dulcoside A	C38H60O17	788.87	6.1 ± 0.4–7.4 ± 0.3	2.03	2.1 ± 0.1	5.0 ± 1.0	–	–	–	0.3 ± 0.01–24.0 ± 0.8	–	–
Rubusoside	C32H50O13	642.73	–	–	5.3 ± 0.2	–	–	–	–	0.3 ± 0.01–23.0 ± 0.6	–	–

^aSeeds of S. rebaudiana were supplied by Mr Andrew Rank (Central Queensland University, Rockhampton, Australia).

^bThe dried Stevia extracts were from European, North American and Chinese suppliers.

^cIt is also known as dulcoside B.

Table 3. Use of stevia leaves and its bioactive compounds in diabetes animal model (N.S., not stated; N.R., not relevant; IVGT, intravenous glucose tolerance; IAGT, intra-arterial glucose tolerance; IPGT, intraperitoneal glucose tolerance; IAGT, intra-arterial glucose tolerance; OGTT, oral glucose tolerance test; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CAT, catalase; GSH, reduced glutathione; SOD, superoxide dismutase; TG, triglycerides).

No.	Reference	Plant part	Tested substance	Animal model	Inducer(mg/kg)	Findings
[1]	Jeppesen et al. (2002)	N.R.	Stevioside (200 mg/kg)	Goto-Kakizaki and Wistar rats	N.R.	During IVGT test, stevioside significantly suppressed glucose response and glucagon levels, but concomitantly increased insulin response in GK rats In normal Wistar rats, stevioside enhanced insulin response without affecting glucagon levels and glucose response Stevioside exerted antihyperglycaemic, insulinotropic, and glucagonostatic actions in the type 2 diabetic rat model
[2]	Jeppesen et al. (2003)	N.R.	Stevioside (25 mg/kg)	Goto-Kakizaki and Wistar rats	N.R.	During IAGT test, stevioside reduced hyperglycemia condition, by enhancing first-phase insulin response and suppressing glucagon levels Stevioside significantly suppressed systolic and the diastolic blood pressure
[3]	Jeppesen et al. (2006)	N.S.	Stevioside (30 mg/kg)	Goto-Kakizaki rats	N.R.	During glucose tolerance test, stevioside-treated animals showed much higher first-phase insulin response and lower glucagon level compared to control animals Stevioside lowered plasma cholesterol level after 5 weeks of treatment
[4]	Suanarunsawata et al. (2004)	Leaves	Aqueous extract (250 mg/kg), Stevioside (250 mg/kg)	Wistar rats	Streptozotocin (40)	Aqueous extract increased insulin level, decreased plasma glucagon level and reduced plasma glucose level in the diabetic group Insulin-induced glucose uptake study using isolated diaphragm muscle revealed suppression action by stevioside in both normal and diabetic rats Stevioside present in stevia extract may indirectly contribute to antihyperglycemic action via potentiating insulin release
[5]	Sumon et al. (2008)	Leaves	Aqueous extract (150, 200, 250 mg/kg)	Albino rats	Streptozotocin (55)	Stevia leaves powder significantly reduced blood glucose levels and possessed hypoglycemic effect at all concentrations
[6]	Saravanan et al. (2012)	N.R.	Rebaudioside A (50, 100, 200 mg/kg)	Albino Wistar rats	Streptozotocin (40)	Rebaudioside A decreased blood glucose, increased the level of plasma insulin and attenuated pancreas damage Reduced activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase while increased hexokinase and glucose-6-phosphate dehydrogenase in the liver along with glycogen in a significant manner
[7]	Shivanna et al. (2013)	Leaves	4% stevia leaves powder, extracted polyhenols and extracted fiber from 4% stevia leaves powder^a	Wistar rats	Streptozotocin (60)	Stevia leaves powder and extracted polyphenols reduced food and water consumption, urine output, blood glucose level while increased serum insulin level Protect against streptozotocin-induced kidney damage and liver damage via decreased glomerular filtration rate and serum level of liver ALT and AST enzymes Antioxidant properties via increased SOD and catalase enzyme activity while reduced lipid peroxidation No changes in stevia fiber-fed rats
[8]	Akbarzadeh et al. (2015)	N.S.	Aqueous extract (250, 500, 750 mg/kg)	Wistar rats	Streptozotocin (60)	Stevia extracts (at a dose rate of 250 and 500 mg/kg) reduced fasting blood sugar, TG, omentin, alkaline phosphatase levels, without changing the number of pancreatic β-cells Stevia extracts decreased the omentin level, possibly by indirectly activating insulin sensitivity and lowering blood glucose
[9]	Assaei et al. (2016)	Leaves	Aqueous extract (400 mg/kg)	Sprague–Dawley rats	Streptozotocin (40)	Aqueous extracts reduced fasting blood sugar, TG, malondialdehyde, ALT and AST levels Normalized lipid peroxidation and catalase activity in the pancreas of the diabetes group treated with stevia (i.e. increased catalase activity and decreased MDA levels compared to the diabetic model group) Aqueous extracts enhanced PPARγ and insulin mRNA levels Histological analysis showed that groups treated with aqueous extracts have relatively better synthesis and aggregation of insulin in the pancreas
[10]	Perumal et al. (2016)	Leaves	Hydro-methanol extract-loaded chitosan nanoparticles (100 mg/kg)	Wistar rats	Streptozotocin (55)	Stevia extract-loaded chitosan nanoparticles reduced fasting blood glucose level Improved diabetic biochemical profiles by reduced glyoxylate hemoglobin level, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and alkaline phosphatases Normalized liver and kidney lipid peroxidation and antioxidant activity of CAT, GSH and SOD. Alleviated streptozotocin-induced pancreatic and liver damage via restoration of hyperplatic islets of Langerhans, hepatocyte hypertrophy and lymphocyte infiltration in the liver
[11]	Ahmad and Ahmad (2018)	Leaves	Aqueous extract (200, 300, 400, 500 ppm/kg)	Albino rats	Streptozotocin (40)	Stevia extract reduced feed and water intakes as well as body weight in diabetic rats Stevia extract decreased blood glucose (random and fasting) and glycosylated hemoglobin level in diabetic rat, which is consistent with increased level of serum insulin and liver glycogen levels
[12]	Ozbayer et al. (2011)	N.S.	Stevia extract (200 mg/kg)	Sprague–Dawley rats	Streptozotocin (60)–nicotinamide (290	Stevia extract increased oxide synthase activity in the kidney Stevia decreased urine glucose level, thereby decreasing urine pH in diabetic rats
[13]	Aranda-González et al. (2016)	N.R.	Rebaudioside B, Rebaudioside C, Rebaudioside D, Dulcoside A, Steviolbioside (20 mg/kg)	Wistar rats	Streptozotocin (65)–nicotinamide (120)	Both acute intraperitoneal and chronic oral administration of rebaudiosides B, C, D, Dulcoside A and Steviolbioside did not exert antihyperglycemic acitivity in IPGT test
[14]	Elhassaneen (2019)	Leaves	Mixture powder (1, 2, 3 and 4% w/w)	Albino rats	Streptozotocin (40)	Stevia leaves powder significantly decreased fasting serum glucose concentration and thiobarbituric reactive substances level in dose-dependent manner
[15]	Kujur et al. (2010)	Leaves	Aqueous, methanolic, ether extracts (2000 mg/kg)	Wistar rats	Alloxan (125)	All stevia extracts significantly decreased the blood glucose level in diabetic rats as tested on the 28th day
[16]	Misra et al. (2011)	Leaves	Benzene:acetone extract (200 and 400 mg/kg)^b	Albino Wistar rats	Alloxan monohydrate (180)	Stevia extract-treated rats attained nearly normal blood glucose level on the 10th day Significant (p < .01) dose-dependent reduction in body weight of alloxan-induced diabetic rats was observed after stevia extract treatment
[17]	Hossain et al. (2011)	Leaves	Petroleum ether, ethyl acetate and chloroform extracts (150 mg/kg)^d	Long–Evans rats	Alloxan (110)	All three extracts (petroleum ether, ethyl acetate and chloroform) reduced the severity of hyperglycemia, enhanced antihyperlipidemic activity and improved glucose tolerance activity
[18]	Sharma et al. (2012)	N.S.	Commercial stevia extract, HERBOCAL (250 mg/kg)	Wistar rats	Alloxan (150)	Stevia extract reduced blood glucose level in diabetic rats, while increased levels of antioxidant enzymes (CAT, SOD, GSH) in the liver and inhibited lipid peroxidation
[19]	Raskovic et al. (2004)	N.R.	Stevita (200 mg/kg), Clear stevioside liquid (20 mg/kg)^c	NMRI Haan mice	Alloxan (100)	Mice pre-treated with Stevita and stevioside did not exhibit significant increase in glycemia after two doses of alloxan Blood glucose concentration of groups pre-treated with stevia and stevioside was lower than control
[20]	Singh et al. (2013)	Leaves	Methanolic extract (300 mg/kg)	Swiss albino mice	Alloxan monohydrate (150)	Group treated with methanolic extract for 21 days showed significant reduction in blood glucose
[21]	Ilić et al. (2017)	N.R.	Stevioside hydrate (20 mg/kg)	NMRI Haan mice	Alloxan (150)	Compared to the diabetic group, stevioside solution prevented the increase in blood glucose during OGTT Stevioside administration conferred certain protective effects against alloxan-induced oxidative damage of the pancreatic β-cells as shown in histopathological studies
[22]	Perumal et al. (2016)	Leaves	Stevioside (0.5, 1.0, 5.0 mg/kg)	Wistar rats	Streptozotocin (60)	Stevioside improved insulin response
					Fructose-rich feed	IPGTT test showed that stevioside reduced plasma glucose (in a dose-dependent manner) and body weight
[23]	Dyrskog et al. (2005)	N.R.	Steviosides (91%), Stevioside supplement (Pure Stevioside, 4% Rebaudioside A, and 5% other glycolsides)(30 mg/kg)	Type 2 diabetic Zucker diabetic fatty rats	N.R.	Combination of stevioside supplement and soy protein lowered blood glucose in IAGT test The combination reduced systolic blood pressure and improved the blood lipid profile after 2 weeks of administration
[24]	Nordentoft et al. (2008)	N.R.	Isosteviol (20 mg/kg)	Diabetic KKAy mice	N.R.	Isosteviol improved glucose homeostasis, increased insulin sensitivity, lowered plasma triglycerides and lowers weight Regulated the gene expression level of key insulin regulatory genes GLUT2, Ins1, Ins2, Pdx1/Ipf1, Beta2/Neurod1, Pax6 and11-beta-HSD-1 and beta-cell transcription factors Nkx2-2, Nkx6-1, C/EBPalpha and FoxA2
[25]	Elnaga et al. (2016)	N.R.	Pure stevia sweetener (25, 250, 500, 1000 mg/kg)	OverweightWistar strain rats	N.R.	Stevia leaves powder and extracted polyphenols reduced food and water consumption, urine output, blood glucose level while increased serum insulin level. Protect against streptozotocin-induced kidney damage and liver damage via decreased glomerular filtration rate and serum level of liver aminotransferase enzymes Antioxidant properties via increased SOD and CAT enzyme activity while reduced lipid peroxidation. No changes in stevia fiber-fed rats
[26]	Aghajanyan et al. (2017)	N.S.	Aqueous extract (100 mg/kg)	Rabbits	Immobilization stress-induced hyperglycemia	Aqueous extract reduced fasting glucose level Lowered atherogenic index via reduced levels of total cholesterol, TG and LDL-cholesterol while increased HDL-cholesterol level Increased liver and muscle glycogen level No differences in body weight and food consumption

^a4.0% stevia leaves powder incorporated diet (4.0 g leaf powder in 96 g dry diet); with equivalent amount of polyphenols extract (through force feeding); with equivalent amount of fiber extracted from 4 g of stevia leaves powder.

^bMean stevioside content was determined to be 0.454% dry leaves weight.

^cThis study is a pre-treatment study using commercially available stevia products from Stevita Co, INC, Arlington Texas and Stevita Co, INC, Herbal supplement, Brazil.

^dThese extracts were derived from ethanolic fraction of stevia leaves.

Table 4. Anti-inflammation activity of stevioside and related compounds (N.S., not stated; N.R., not relevant; TPA, 12-O-tetradecanoylphorbol-13-acetate; ID₅₀, half maximum inhibitory dose; LPS, lipopolysaccharides; qRT-PCR, quantitative real-time PCR; MPO, Myeloperoxidase; ELISA, enzyme-linked immunosorbent assay; IHC, Immunohistochemistry; Nrf2, nuclear factor (erythroid-derived 2)-like 2; TAA, thioacetamide).

No.	References	Plant part	Tested substance	Experimental design	Dosage and results
[1]	Yasukawa et al. (2002)	N.R.	Stevioside^a, Rebaudioside A^a, Rebaudioside C^a, Dulcoside A^a, Stevioside mixture^b (0.1– 1.0 mg/mouse)	In vivo – mice (skin tumor induced by TPA)	Inhibited inflammation with ID50 for each substance to be: (a) Stevioside, 291.6 µg/ear, (b) Rebaudioside A, 92.2 µg/ear, (c) Rebaudioside C, 92.2 µg/ear, (d) Dulcoside A, 92.5 µg/ear, (e) Stevioside mixture, 239.9 µg/ear Stevioside prevented skin tumor formation
[2]	Mizushina et al. (2005)	N.R.	Stevioside^c, Isosteviol^c, Steviol^c	In vitro – DNA polymerase assaysIn vitro – human T-cell acute lymphoblastic leukemia cell line (MOLT-4); In vivo – mice (ear inflammation)	Inhibited production of DNA metabolic enzymes, human cancer cell growth and inflammatory ear edema IC50 values of isosteviol for calf DNA polymerase α and human DNA polymerase λ were 64.0 and 103 µM, respectively LD50 value of isosteviol for MOLT-4 was 84 µM At 500 µg/ear, isosteviol reduced inflammation by 53.0 (±4.8) % (compared to TPA only group)
[3]	Boonkaewwan et al. (2006)	Leaves	Stevioside (1 mM), Steviol (0.1–100 µM)	In vitro – human monocytes cell line (THP-1), ELISA, Western blot	Attenuated inflammatory mediators’ synthesis by inhibiting IκBα/NF-κB signaling pathway Stevioside suppressed LPS-induced release of TNF-α and IL-1β and nitric oxide, but not steviol Only stevioside induced TNF-α, IL-1β, and nitric oxide release in unstimulated THP-1 cells
[4]	Bunprajun et al. (2012)	N.R.	Stevioside (10 mg/kg)	In vivo – rat (muscles)	Enhanced satellite cell activation by inhibiting NF-κB signaling pathway Reduced NF-κB nuclear translocation
[5]	Fengyang et al. (2012)	N.S.	Stevioside (50, 100 and 200 µg/ml)	In vitro – human macrophage cell lines (RAW264.7), ELISA, qRT-PCR, western blot	Suppressed TNF-α, IL-6, and IL-1β gene expression and protein levels in LPS-stimulated RAW264.7 cells in a dose-dependent manner Reduced NF-κB activation, IκBα degradation, phosphorylation of ERK, JNK and p38 protein level
[6]	Boonkaewwan and Burodom (2013)	Leaves	Stevioside (0.01–1 mmol/l), Steviol (1-100 µmol/l)	In vitro – human colon carcinoma cell line (Caco-2), ELISA	Attenuated cytokine gene expression via IκBα/NF-κB signaling pathway Suppressed TNF-α, IL-1β and IL-6 release Increased IκBα activation and inhibited NF-κB expression at protein level
[7]	Yingkun et al. (2013)	N.R.	Stevioside (12.5, 25 and 50 mg/kg)	In vivo – mice (lung), ELISA, MPO and nitrate/nitrite content assay, western blot	Attenuated histological alterations in the lung Stevioside and dexamethasone significantly decreased the number of inflammation cells. Reduced TNF-α, IL-6, and IL-1β protein levels Inhibited the phosphorylation of IκB-α and NF-κB Decreased protein expressions of iNOS and COX-2
[8]	Wang et al. (2014a)	Leaves	Stevioside (30, 100 and 300 µg/ml)	In vitro – primary mouse mammary epithelial cells (MMECs), ELISA, qRT-PCR, western blot	Suppressed the activation of the NF-κB and MAPK pathways in Staphylococcus aureus-infected MMECs Decreased TLR2 gene expression Decreased TNF-α, IL-6, and IL-1β gene and protein expression
[9]	Wang et al. (2014b)	Leaves	Stevioside (33, 100 and 300 mg/kg)	In vivo – mice (mammary glands), ELISA, qRT-PCR, western blot	Inhibited inflammation by regulating the NF-κB and MAPK pathways in Staphylococcus aureus-infected mouse mammary glands Suppressed the NF-κB pathway by prominently inhibiting the phosphorylation of IκBα and p65 protein Inhibited the increase of phosphorylated p38, ERK and JNK. Reduced expression of TNF-α, IL-1β, and IL-6 at gene and protein levels Suppressed TLR2 mRNA levels
[10]	Holvoet et al. (2015)	Leaves	Stevioside (10 mg/kg), Rebaudioside A (12 mg/kg), Steviol (5 mg/kg)	In vivo – mice (liver)^d, qRT-PCR	Attenuated hepatic steatosis extent by effecting glucose and lipid metabolism, inflammation and oxidative stress Decreased the gene expression of NF-κB
[11]	Latha et al. (2017)	Leaves	Hydroalcoholic extract of stevia (in vivo – 500 mg/kg), Stevioside (in vivo – 250 mg/kg)	In vitro – DPPH, nitric oxide radical scavenging activity, superoxide radical scavenging activity; In vivo – rat (liver), ELISA	IC50 values of stevioside and hydroalcoholic extract of stevia for DPPH assay were found to be 156.8 and 138.33 µg/ml, respectively IC50 values of stevioside and hydroalcoholic extract of stevia for nitric oxide radical scavenging assay were found to be 102.55, 78.71 µg/ml, respectively IC50 values of stevioside and hydroalcoholic extract of stevia for superoxide radical scavenging assay were found to be 134.6, 107.72 µg/ml, respectively Reduced hepatic oxidative stress and attenuated structural changes Reduced TNF-α, IL-1β and IL-6 release Increased protein levels of superoxide dismutase and glutathione in LPS-induced rats
[12]	Ramos-Tovar et al. (2018a)	Leaves	Aqueous extract of stevia (100 mg/kg)	In vivo – rat (liver), ELISA, IHC	Ameliorated oxidative stress, necrosis as well as cholestasis and preserved hepatic architecture against TAA-induced cirrhosis Prevented liver inflammation by downregulating NF-κB expression and partially preserved protein expression of Nrf2 Reduced protein expression of TNF-α, IL1-β, IL-6, IL-10
[13]	Ramos-Tovar et al. (2018b)	Leaves	Stevia mixture^e (100 mg/kg)	In vivo – rat (liver), IHC, western blot, qRT-PCR	Prevented acute carbon tetrachloride-induced glutathione depletion and lipid peroxidation Prevented necrosis and inflammation via decreasing expression of NF-κB and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10)
[14]	Meng et al. (2018)	N.R.	Stevioside (in vitro – 200 µM; in vivo –10, 30 mg/kg)	In vitro – bone marrow-derived macrophages (BMMs); In vivo – mice	Suppressed titanium particle-induced NF-κB and MAPK signaling pathways through inhibition of TAK1 phosphorylation Inhibited production of nitric oxide and prostaglandin E2 stimulated by titanium particles Reduced the mRNA and protein expression of TNF-α, IL-6 and IL-1β
[15]	Casas-Grajales et al. (2019a)	N.S.	Stevioside (in vitro – 5, 10, 20 and 40 mM; in vivo – 20 mg/kg)	In vitro – Human HSCs, western blot, qRT-PCR, DPPH; In vivo – rats (liver and blood), IHC, western blot, qRT-PCR, DPPH	Preserved body weight, liver/body weight ratio, glycogen content; ameliorated oxidative stress against TAA-induced cirrhosis. Prevented inflammation by reducing NF-κB and pro-inflammatory cytokines (IL-17a, TNF-α, IL-1β, IL-6 and IL-10) at both gene and protein levels Improved the cellular redox state by preserving Nrf2 expression
[16]	Casas-Grajales et al. (2019b)	N.R.	Rebaudioside A (in vitro – 1, 5, 10, 20 and 100 mM; in vivo – 20 mg/kg)	In vitro – Human HSCs, western blot, qRT-PCR, DPPH; In vivo – rats (liver and blood), IHC, western blot, qRT-PCR, DPPH	Prevented fibrogenesis, morphological, histological and biochemical changes against TAA-induced cirrhosis Ameliorated oxidative stress by preserving protein expression of Nrf2 Prevented liver inflammation by downregulating NF-κB and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) Reduced expression of α-SMA, TGF-β1, Smad7 and MMP-13 protein

^aVaried doses of steviol glycosides (0.008, 0.04, 0.2 or 1.0 mg/ear) were used to study anti-inflammatory activity against TPA-induced inflammation.

^bStevioside mixture contains stevioside (48.9%), rebaudioside A (24.4%), rebaudioside C (9.8%), dulcoside A (5.6%) and unidentified components (11.3%).

^cTwo different doses of compounds were used at 250 or 500 µg/ear.

^dob/ob and LDLR-double deficient mice was used for the study.

^eAuthors used commercially available stevia which is procured as Mayan Sweet Stevia® (Yucatan, Mexico).

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Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.